Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
PLoS One. 2011;6(11):e27384. doi: 10.1371/journal.pone.0027384. Epub 2011 Nov 11.
IRF8 (Interferon Regulatory Factor 8) is a transcription factor expressed throughout B cell differentiation except for mature plasma cells. Previous studies showed it is part of the transcriptional network governing B cell specification and commitment in the bone marrow, regulates the distribution of mature B cells into the splenic follicular and marginal zone compartments, and is expressed at highest levels in germinal center (GC) B cells. Here, we investigated the transcriptional programs and signaling pathways affected by IRF8 in human and mouse GC B cells as defined by ChIP-chip analyses and transcriptional profiling. We show that IRF8 binds a large number of genes by targeting two distinct motifs, half of which are also targeted by PU.1. Over 70% of the binding sites localized to proximal and distal promoter regions with ∼25% being intragenic. There was significant enrichment among targeted genes for those involved in innate and adaptive immunity with over 30% previously defined as interferon stimulated genes. We also showed that IRF8 target genes contributes to multiple aspects of the biology of mature B cells including critical components of the molecular crosstalk among GC B cells, T follicular helper cells, and follicular dendritic cells.
IRF8（干扰素调节因子 8）是一种在 B 细胞分化过程中表达的转录因子，除成熟浆细胞外均有表达。先前的研究表明，它是控制骨髓中 B 细胞特异性和定向的转录网络的一部分，调节成熟 B 细胞在脾脏滤泡和边缘区隔室中的分布，并且在生发中心（GC）B 细胞中表达水平最高。在这里，我们通过 ChIP-chip 分析和转录谱分析研究了 IRF8 在人和小鼠 GC B 细胞中影响的转录程序和信号通路。我们表明，IRF8 通过靶向两个不同的基序结合大量基因，其中一半也被 PU.1 靶向。超过 70%的结合位点定位于近端和远端启动子区域，其中约 25%是基因内的。在靶向基因中，有大量与先天和适应性免疫相关的基因富集，其中超过 30%以前被定义为干扰素刺激基因。我们还表明，IRF8 的靶基因有助于成熟 B 细胞生物学的多个方面，包括 GC B 细胞、滤泡辅助性 T 细胞和滤泡树突状细胞之间分子串扰的关键组成部分。
